Lipid nanoparticles as oral vehicles of immunotherapy

a technology of lipid nanoparticles and immunotherapy, which is applied in the direction of drug compositions, peptide/protein ingredients, metabolic disorders, etc., can solve the problems of t1d autoreactivity development that is much longer, remains quite elusive, and is not easy to be detected and treated, and achieves the potential for local and systemic pathophysiologic effects, low bioavailability, and low bioavailability

Pending Publication Date: 2022-10-27
THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Differently from transplantation, where the timing of exposure to antigens is well defined, the development of autoreactivity in diseases like T1D spans a much longer period and remains quite elusive.
Unfortunately, administration of native insulin by this route leads to rapid enzymatic degradation in the stomach and intestinal lumen, resulting in low bi

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Lipid nanoparticles as oral vehicles of immunotherapy
  • Lipid nanoparticles as oral vehicles of immunotherapy
  • Lipid nanoparticles as oral vehicles of immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0111]Targeted Jak inhibition synergizes with CoB to prolong transplant survival.

[0112]The feasibility of combining CTLA4-Ig with a short-course Tofa administration in a full MHC mismatch (C57BL / 6 to BALB / c) mouse heart transplantation model was tested (FIG. 1A). Encouragingly, heart transplant survival in mice treated with CTLA-4Ig was significantly improved by a short course (10 days) of Tofa (MST untreated: 9d, CTLA4-Ig only: 36d, Tofa+CTLA4-Ig: 120d). This improvement was evident even in mice receiving hearts kept ischemic for 4 h before transplantation—a more clinically relevant scenario—where CTLA4-Ig efficacy is undermined by early accumulation of inflammatory mediators67 (MST untreated: 9d, CTLA4-Ig only: 26.5d, Tofa+CTLA4-Ig: 150d). Analysis of the graft infiltrate by flow cytometry revealed that the protective effect of the combination of Tofa+CTLA4-Ig was associated the accumulation of a much higher frequency of Treg cells (FIG. 1B). Moreover, ex-vivo restimulation of spl...

example 2

[0113]Targeted Jak inhibition limits DC maturation.

[0114]To better understand the impressive protective effect achieved with the combination Tofa+CTLA4-Ig, we tested the ability of Tofa to inhibit the maturation of bone marrow derived dendritic cells (DC) in response to LPS (FIG. 2). Exposure to Tofa caused a significant inhibition of the up-regulation of CD80 and CD86 costimulatory molecules, with a concomitant reduction in release of the prototypical inflammatory cytokines IL-6 (not shown), IL-1, and TNF-α. The latter two have been implicated in T1D development and inhibition of their accumulation would be a valuable effect. Interestingly, Tofa did not prevent the up-regulation of MHC-II molecules, rendering DC with high Signal 1 but very low Signal 2 (costimulatory molecules) and low Signal 3 (cytokines)—a phenotype that could maximize the impact of CTLA4-Ig on reactive T cells.

example 3

[0115]Tofa does not interfere with Treg suppression of T cells.

[0116]The observed accumulation of Treg in transplants treated with Tofa+CTLA4-Ig warranted confirmation that Tofa (although transient) would not interfere with Treg function. The results of a T cell CFSE-Proliferation-Assay conducted to assess the suppressive activity of Treg (added at either 2:1 or 4:1 T cell to Treg ratio) without and with Tofa (at 0.5 or 1 μM) confirmed the preservation of regulatory activity (FIG. 3). These results show the potential of the combined use of Tofa with CTLA4-Ig for induction of long-term regulation.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

Lipid nanoparticle compositions for use in immunomodulation and treatment of autoimmune and related diseases such as Type 1 Diabetes are provided along with methods for using same.

Description

REFERENCE TO RELATED APPLICATIONS[0001]This application is a § 371 U.S. National Entry Application of PCT / US2020 / 026574, filed Apr. 3, 2020, which claims the benefit of U.S. Provisional Patent Application No. 62 / 828,743, filed on Apr. 3, 2019 and U.S. Provisional Patent Application No. 62 / 858,775, filed on Jun. 7, 2019, each of which are hereby incorporated by reference for all purposes as if fully set forth herein.STATEMENT OF GOVERNMENTAL INTEREST[0002]This invention was made with government support under grant HL127355 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Autoimmune diseases are pathologies caused by the erroneous attack of a patient immune system against an organ or tissues of the own body. Autoimmune diseases are often treated with immunosuppressants that weaken the entire immune system, leaving patients vulnerable to infection. An ideal autoimmune therapy establishes immune tolerance t...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K9/51A61K31/519A61K31/541A61K38/28
CPCA61K9/5123A61K31/519A61K31/541A61K38/28A61P3/10B82Y5/00A61K9/1075A61K9/0053
Inventor RAIMONDI, GIORGIOPATRONE, JULIACALDERON-COLON, XIOMARATIBURZI, OLIVIA
Owner THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap